We are investigating environmentally responsive human placental enzymatic activities. Two systems are currently being studied; microsomal xenobiotic oxidation, and cytosolic glutathione S-transferase activity. Responses to active and passive maternal smoking during pregnancy have been documented. Genetic contributions to variability in activities are being assessed under various environmental conditions using twin-study methodology. Placental activities from both normal and abnormal pregnancies are also being characterized prospectively after ascertainment of in utero maldevelopment by ultrasound. In these investigations characterization of placental xenobiotic oxidation involves measurement of activities in vitro toward substrates sucha as benzo(a)pyrene, 7-ethoxyresorufin, and caffeine; response to various inhibitors of microsomal oxygenase activity (e.g., 7,8-benzoflavone); and solubilization, separation, and reconstitution of molecular components of placental microsomal cytochrome P-450 systems.